rs10947262

Positions:

• chr6-32405535-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001304561.2(BTNL2):​c.80-249G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 535,802 control chromosomes in the GnomAD database, including 5,447 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1361 hom., cov: 32)
  • Exomes 𝑓: 0.12 (4086 hom.)
• Consequence: BTNL2 NM_001304561.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.47

Genes affected

BTNL2 (HGNC:1142): (butyrophilin like 2) This gene encodes a major histocompatibility complex, class II associated, type I transmembrane protein which belongs to the butyrophilin-like B7 family of immunoregulators. It is thought to be involved in immune surveillance, serving as a negative T-cell regulator by decreasing T-cell proliferation and cytokine release. The encoded protein contains an N-terminal signal peptide, two pairs of immunoglobulin-like domains, separated by a heptad peptide sequence, and a C-terminal transmembrane domain. Naturally occurring mutations in this gene are associated with sarcoidosis, rheumatoid arthritis, ulcerative colitis, inflammatory bowel disease, myositis, type 1 diabetes, systemic lupus erythematosus, acute coronary syndrome, and prostate cancer. [provided by RefSeq, May 2017]

TSBP1-AS1 (HGNC:39756): (TSBP1 and BTNL2 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTNL2	NM_001304561.2	c.80-249G>A		intron_variant		ENST00000454136.8	NP_001291490.1
TSBP1-AS1	NR_136245.1	n.384C>T		non_coding_transcript_exon_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTNL2	ENST00000454136.8	c.80-249G>A		intron_variant		5	NM_001304561.2	ENSP00000390613	P1
TSBP1-AS1	ENST00000645134.1	n.833C>T		non_coding_transcript_exon_variant	4/5

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18558 AN: 152054 Hom.: 1358 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.0786

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0817

Gnomad OTH AF: 0.135

GnomAD4 exome AF: 0.122 AC: 46660 AN: 383630 Hom.: 4086 Cov.: 2 AF XY: 0.123 AC XY: 25416 AN XY: 206256

Gnomad4 AFR exome AF: 0.132

Gnomad4 AMR exome AF: 0.175

Gnomad4 ASJ exome AF: 0.0849

Gnomad4 EAS exome AF: 0.354

Gnomad4 SAS exome AF: 0.166

Gnomad4 FIN exome AF: 0.168

Gnomad4 NFE exome AF: 0.0817

Gnomad4 OTH exome AF: 0.115

GnomAD4 genome AF: 0.122 AC: 18571 AN: 152172 Hom.: 1361 Cov.: 32 AF XY: 0.128 AC XY: 9548 AN XY: 74398

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.0786

Gnomad4 EAS AF: 0.308

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.0816

Gnomad4 OTH AF: 0.134

Alfa AF: 0.0919 Hom.: 1484

Bravo AF: 0.118

Asia WGS AF: 0.221 AC: 768 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.38
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10947262; hg19: chr6-32373312;